Emerging roles of ATG proteins and membrane lipids in autophagosome formation

Nishimura, Taki; Tooze, Sharon A.

doi:10.1038/s41421-020-0161-3

Cited by 198 publications

(151 citation statements)

References 242 publications

(352 reference statements)

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“…Autophagosome formation is driven by the autophagy-related (ATG) proteins that are both spatially and temporally controlled and are divided into distinct units: ULK complex, the class III phosphatidylinositol 3-kinase (PI3K) complex, the ATG2-ATG18/WIPI4 complex, ATG9, the ATG12 conjugation system and the ATG8/LC3 conjugation system ( Nishimura and Tooze, 2020 ).…”

Section: Autophagy: An Overviewmentioning

confidence: 99%

Autophagy and Exosomes Relationship in Cancer: Friends or Foes?

Colletti

Ceglie

Giannatale

et al. 2021

Front. Cell Dev. Biol.

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Autophagy is an intracellular degradation process involved in the removal of proteins and damaged organelles by the formation of a double-membrane vesicle named autophagosome and degraded through fusion with lysosomes. An intricate relationship between autophagy and the endosomal and exosomal pathways can occur at different stages with important implications for normal physiology and human diseases. Recent researches have revealed that extracellular vesicles (EVs), such as exosomes, could have a cytoprotective role by inducing intracellular autophagy; on the other hand, autophagy plays a crucial role in the biogenesis and degradation of exosomes. Although the importance of these processes in cancer is well established, their interplay in tumor is only beginning to be documented. In some tumor contexts (1) autophagy and exosome-mediated release are coordinately activated, sharing the molecular machinery and regulatory mechanisms; (2) cancer cell-released exosomes impact on autophagy in recipient cells through mechanisms yet to be determined; (3) exosome-autophagy relationship could affect drug resistance and tumor microenvironment (TME). In this review, we survey emerging discoveries relevant to the exosomes and autophagy crosstalk in the context of cancer initiation, progression and recurrence. Consequently, we discuss clinical implications by targeting autophagy-exosomal pathway interaction and how this could lay a basis for the purpose of novel cancer therapeutics.

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Section: Autophagy: An Overviewmentioning

confidence: 99%

Autophagy and Exosomes Relationship in Cancer: Friends or Foes?

Colletti

Ceglie

Giannatale

et al. 2021

Front. Cell Dev. Biol.

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“…Once fused, acidic hydrolases in the lysosome can degrade the autophagic cargos and salvaged nutrients are released to the cytoplasm to be recycled by cells (Rong et al, 2012;Yu et al, 2018;Zhao and Zhang, 2019). The detailed molecular mechanisms of these proteins regulating different steps in autophagy have been recently reviewed in separate papers (Carlsson and Simonsen, 2015;Nakamura and Yoshimori, 2017;Reggiori and Ungermann, 2017;Dikic and Elazar, 2018;Mercer et al, 2018;Yu et al, 2018;Lai et al, 2019;Osawa et al, 2019a;Zhao and Zhang, 2019;Melia et al, 2020;Nishimura and Tooze, 2020). In Table 2, we summarized all of the known membrane-associated proteins, their functions, and their membrane-binding mechanisms in all steps of autophagy in a spatiotemporal way.…”

Section: Membrane-associated Proteinsmentioning

confidence: 99%

Lipids and membrane-associated proteins in autophagy

Tong

et al. 2020

Protein Cell

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Autophagy is essential for the maintenance of cellular homeostasis and its dysfunction has been linked to various diseases. Autophagy is a membrane driven process and tightly regulated by membrane-associated proteins. Here, we summarized membrane lipid composition, and membrane-associated proteins relevant to autophagy from a spatiotemporal perspective. In particular, we focused on three important membrane remodeling processes in autophagy, lipid transfer for phagophore elongation, membrane scission for phagophore closure, and autophagosome-lysosome membrane fusion. We discussed the significance of the discoveries in this field and possible avenues to follow for future studies. Finally, we summarized the membrane-associated biochemical techniques and assays used to study membrane properties, with a discussion of their applications in autophagy.

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“…Among the ATG proteins, ATG9A is the only transmembrane protein within the autophagy core machinery and it is essential for the initiation of autophagosome formation. Even if its precise role in autophagy remains elusive, it is thought to act by supplying components, such as proteins and lipids, to the autophagosomal membranes ( 15 , 25 ).…”

Section: Overview Of the Process Of Autophagymentioning

confidence: 99%

Regulation of Innate Immune Responses by Autophagy: A Goldmine for Viruses

2020

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Autophagy is a lysosomal degradation pathway for intracellular components and is highly conserved across eukaryotes. This process is a key player in innate immunity and its activation has anti-microbial effects by directly targeting pathogens and also by regulating innate immune responses. Autophagy dysfunction is often associated with inflammatory diseases. Many studies have shown that it can also play a role in the control of innate immunity by preventing exacerbated inflammation and its harmful effects toward the host. The arms race between hosts and pathogens has led some viruses to evolve strategies that enable them to benefit from autophagy, either by directly hijacking the autophagy pathway for their life cycle, or by using its regulatory functions in innate immunity. The control of viral replication and spread involves the production of anti-viral cytokines. Controlling the signals that lead to production of these cytokines is a perfect way for viruses to escape from innate immune responses and establish successful infection. Published reports related to this last viral strategy have extensively grown in recent years. In this review we describe several links between autophagy and regulation of innate immune responses and we provide an overview of how viruses exploit these links for their own benefit.

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Emerging roles of ATG proteins and membrane lipids in autophagosome formation

Cited by 198 publications

References 242 publications

Autophagy and Exosomes Relationship in Cancer: Friends or Foes?

Autophagy and Exosomes Relationship in Cancer: Friends or Foes?

Lipids and membrane-associated proteins in autophagy

Regulation of Innate Immune Responses by Autophagy: A Goldmine for Viruses

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